In a cross-national study, we propose to investigate etiological heterogeneity in autism by focussing on disorders in the first degree relatives of autistic probands which may be genetically associated with autism and thus, may represent a genetic predisposition to autism. 220 families will be ascertained through a school-aged autistic child (110 from each site). The autistic probands will be stratified by sex and IQ, and characterized according to their early environmental history, and clinical features and tested for fragile-X. Their first degree relatives will be examined to detect cognitive abnormalities (mental retardation, language delay and reading disability), abnormalities of social relatedness, and the major psychiatric disorders, (affective disorder and schizophrenia). The first degree relatives of 80 children with Down's syndrome (40 at each site), matched on relevant variables, and the first degree relatives of 40 adopted autistic children, (20 at each site), will be similarly studied to establish base rates of the proposed "associated" abnormalities as they occur in families of children handicapped by a condition known to be genetically absent from the other family members. The major hypotheses of the study are that mental retardation, language delay, reading disability, and abnormalities of social relatedness, but not the major psychiatric disorders, will be more common among the family members of autistic probands than among the family members controls; that within the families of autistic children, these abnormalities will be less frequent among family members of autistic probands who suffered from environmental injuries (infectious or traumatic); that the abnormalities of reading ability, language delay and social relatedness will be more common among family members of autistic probands with higher IQa ("pure autism"), and that mental retardation, on the other hand, will be more common among family members of autistic probands with low IQs; and finally, that Fragile-X will explain some but not all of the familial loading in autism.